This invention relates to methods for the synthesis of metallocenes.
Amino-functionalised titanocenes are of increasing interest because of their potential to act as highly active and selective olefin polymerisation catalyst precursors [1,2,3,4]. The neutral amino function can reversibly co-ordinate to the metal centre, potentially stabilising highly reactive intermediates formed during homogeneous catalytic processors. High catalytic activity has been found with group IV metallocenes as well as with metallocenes involving other metals. For instance, half-sandwich complexes of chromium in which the pendant amino function is co-ordinated to the metal centre have been shown to be highly active olefin polymerisation catalysts [5]. Furthermore, the pendant amino function can interact with inorganic support materials, thereby incorporating traditional metallocene catalysts into heterogeneous catalysts.
Quaternisation of the pendant amino group can result in water stable and soluble species [1,2,4]. Such species may not only provide water soluble catalytic compounds but are also useful as anti-tumour drugs having advantages over the known anti-tumour drug titanocene dichloride. Although titanocene dichloride is an efficient anti tumour agent [6,7], it has low solubility and is unstable in aqueous solution. The greater stability and solubility of amino-functionalised titanocenes renders these materials, and their dihydrochloride derivatives, potentially more suitable as anti-tumour agents as well as providing more suitable models for studying the mechanism of action of titanocene dichloride as an anti tumour agent
Known synthetic methods for the preparation of the dihydrochloride salts of amino-functionalised titanocenes involve the deprotonation of the neutral cyclopentadiene to give lithium, sodium or thallium salts [2,3,4]. In situ deprotonation can be achieved by the addition of an external base [8]. The reaction of the metal salt with TiCl4 results from the formation of the neutral metallocene which is then reacted with HCl to give the dihydrochloride salt Accordingly such a process involves 3 steps from the cyclopentadiene to the dihydrochloride salt. There is a need for an improved process involving fewer steps and producing the dihydrochloride salt in relatively high yield.
According to the present invention there is provided a method for the preparation of a metallocene halide salt having at least one cyclopentadiene group substituted by a basic group, said method comprising reacting together a metal halide with a cyclopentadiene substituted by said basic group.
Accordingly the present invention provides a single step process for the preparation of an amino-functionalised metallocene which can be produced in high yield. It is believed that this single step process is possible because the method utilises the presence of an xe2x80x9cinternal basexe2x80x9d rather than by making use of an external base in the known 3 step process.
The method of the present invention may be applied to the preparation of metallocenes of both early and late transition metals including the group IV metals Ti, Zr and Hf.
Preferably the metal halide is a homoleptic halide, more preferably a homoleptic chloride, an example being TiCl4.
Preferably the substituted cyclopentadienyl carries a pendant Lewis base. More preferably the Lewis base is provided by an amino group, for instance, a tertiary amino group, examples being xe2x80x94CH2CH2N(CHCH3)2 and xe2x80x94CH2CH2N(CH2)5.
Preferably the cyclopentadienyl is contacted with the metal halide in the presence of an inert solvent such as toluene.
Preferably the substituted cyclopentadiene and the metal halide are reacted together at ambient temperature or below. One reactant may be added to the other in a dropwise fashion. The addition may be carried out more quickly the lower the temperature.
The metallocene halide salt prepared by the method of the present invention may be converted to the neutral metallocene by contacting the salt with a base. Furthermore the metallocene halide salt may be converted to other species. For example, contacting the metallocene halide salt with an alkylating agent results in the formation of an alkyl substituted metallocene.
The method of the present invention represents a new and facile route to metallocene halide salts in high yield. The method is therefore highly advantageous over the known three steps synthetic routes.